The fundamental goal of this proposal is the elucidation of the mechanisms underlying the process of synaptic transmission in the mammalian central nervous system. One reason for the recurrent difficulty in the identification of neurotransmitters and in the interpretation of the actions of psychoactive drugs has been the competition which exists between excitatory and inhibitory influences impinging upon the neurons of adult animals. There is evidence that synaptic connections in some brain areas develop slowly during postnatal life. For example, we reported that the dopamine concentrating mechanisms in cat caudate nucleus are poorly represented for several weeks after birth, suggesting that the depressant effects of the dopaminergic projection to caudate neurons is absent or very weak during early growth. Thus, the nature of excitatory mechanisms in the caudate and the role of acetylcholine, which are not understood at present, may be more amenable to study during maturation than at the adult stage. In the immature hippocampus of the rat we found, by a variety of histochemical and analytical techniques, that zinc accumulates rapidly in the mossy fiber terminals on the dentrites of CA3-4 pyramidal cells between 18 and 22 days after birth. Other workers have reported distinct morphological and functional changes in hippocampal projections during development. The possible function of zinc as an essential component in neurotransmission, and its relationship to hippocampal function has not been previously explored. We propose, then to study synaptic transmission in neonatal and developing caudate and hippocampus, using microiontophoretic application of suspected transmitters and receptor blockers, coupled with electrical stimulation of brain areas which may evoke excitatory responses at the single neuron level of integration.